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SC BIOL 610 - Quiz 1 Study Guide

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Biol 610 1st EditionQuiz # 1 Study Guide Lectures: 1 – 12Proto-oncogenes- class of gene that controls the checkpoints that can initiate cancer developments if a mutation occurs1. Encode proteins that start or maintain cell growth and division 2. When genes are on, cells grow and divide3. Mutation in this genes cause it to be permanently ON in cancer or over produce the proteins they encode 4. Mutation in this gene is called oncogenes a. Requires other mutations including one in a tumor suppressor gene i. Ex: ras genes that regulate cell growth and division Properties shared by all forms of cancer1. Higher than normal rate of mutations 2. Abnormalities in chromosome structure and number 3. One or more forms of genomic instability a. Increased chromosomal changes as cancer developsi. Loss of chromosomes ii. Duplication of chromosomes iii. Deletion of chromosomes b. Instability to repair DNA damage i. Breast cancer: BRCA1 and BRCA2ii. Colon cancer: MSH2 and MLH1Cancer can result from defects in genes that encode DNA repair enzymes that maintain the integrity of the genomeDarwinian Evolution can be explained by Mendelian Genetics 1. 1920-30: Genetic information can be altereda. Mutations – responsible for changing genetic informationi. Converts one allele into anotherii. Create a new allele from an allele that was previously widespread within a certain speciesConsequences of silent or neutral mutations 1. Non-coding DNA change more rapidly than coding DNA sequencesa. GENETIC POLYMORPHISMi. Inter-individual functionally silent differences in DNA sequence that make each human genome uniqueii. Heritable sequences from both parentsAdvantage of having two redundant gene copies:1. If one copy is mutationally inactivated, the surviving copy can still specify a wild type phenotype2. Importance in cancer development:a. Almost all genes that function to prevent unregulated proliferation are present a redundant pairsi. Both copies must be inactivated to lose their growth-suppressing functions and allow malignant growth to occurHow Normal Cells can be transformed into Cancer Cells1. Alterations in Genes, Chromosomes and Signaling/Metabolic Pathways2. Genetic aberrations that lead to cancer:a. Mutationsb. Alterations in chromosomesi. Loss of entire chromosomeii. Presence of extra copiesiii. Fusion of one arm with part of another 3. Aneuploidy- observed in cancer cellsIncreases and Decreases in the copy number of chromosomes or chromosomal segments 1. Homogenously staining regions (HSR)a. Amplification in the copy number of genes i. Chromosome segments are copied multiple times over ii. Extra copies can be fused head-to-tail in long arrays 1. Ex: amplification of myc oncogene in human endocrine tumor b. Double-minute chromosomes (DMs)i. Derived from chromosomal segments that have broken loose from original siteii. Replicated many times as extra or sub-chromosomal genetic elements1. Duplicated during mitosis like normal chromatids2. Results in increase in copy number and expression of genes a. Ex: HER2/new oncogene duplicated and amplified in DMs in mouse breast cancer cellc. Both amplified genes in HSRs and in DMs can co-exist within the same celli. Ex: amplification of my oncogene within chromosome in COLO320 humancolorectal adenocarcinoma cellsd. Deleted regions can be detected by fluorescence in situ hybridization (FISH)i. Growth inhibiting genes are discarded by cancer cells during their development ii. Intrachromosomal probes for FISH indicate deleted region in normal chromosome 5 after extensive exposure to radiation form plutonium1. Ex: loss of growth-inhibiting genes can cause proliferation of cancer cells Cancer causing mutations can occur in both germ line and somatic cells1. Somatic mutation- affect only the particular cell with mutation but WILL NOT be transmitted to the offspring a. Responsible for majority of cancer formation i. Affects behavior of cellii. Repeated rounds of cell growth and division pass mutation to all descendant within a tissue1. Constitute clone derived from a single cell Proteins are subject to post-translation modifications 1. Covalent modifications on specific amino acid residues:a. Phosphorylation – attachment of phosphate groups to serine, threonine, or tyrosine amino acid residuesi. signal transductionb. Addition of complex sugar chains – glycosylationi. Mostly on secreted proteinsc. Methylation or acetylationi. Histone proteins in nucleosomes that are wrapped around DNA; control access to genes by RNA polymerase during transcriptiond. Addition of lipid groups2. Cleavage of proteins by proteasesa. Short amino acid sequences within the secreted proteins determine their specificintracellular localizationi. Usually cleaved upon arrival at their destinationb. Pre-cursor proteins are cleaved to activate other proteins in a signal transduction cascadeAlternative Splicing 1. Tissue specific alternative splicing of α-tropomyosin pre-mRNAa. Each mRNA product encodes an important component of cell contractilityb. 95% of pre-mRNAs from the human genes undergo alternative splicing2. Impact of alternative splicing in cancer cellsa. splicing patterns may be different from those in normal cells i. generate protein isoforms that are not found in normal cellsii. Affect untranslated regions of mRNA that may be targeted by micro RNA1. May alter the function of mRNA by altering its stability or translation3. SRSF6 - protein that specifies alternative splicinga. overexpressed in skin cancer cells b. Favors transformation (conversion) of cells from normal to cancerousc. Promotes invasion and metastasis by alternative splicing of Tenascin C mRNAMicroarray Analysis 1. allows assessment of global gene expression in particular cell types2. Comparison of gene expression patterns of different types of cancersGene cloning – genomes can be cut into smaller pieces and cloned1. Generate genomic librariesa. Hybridization techniques allowed identification of fragments from the library thatcontained the gene of interest2. Generate DNA copies of mRNA a. Discovery of the enzyme reverse transcriptaseb. Allowed the synthesis of complementary DNA molecules (cDNA)i. Carry the information in the mRNA after all introns have been removed by splicing3. Use of restriction enzymes allowed construction of plasmids used to generate millions ofcopies of the cDNA clone, express the gene an proteins that are encodedCOLLECTIVE IMPACT OF POST-TRANSCRIPTIONAL REGULATION OF GENE EXPRESSION1.


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